<p>α-Oxy carbonyl compounds, characterized by their distinct electronic and topological properties, represent highly versatile building blocks and modifiers for functional molecules. Despite their potential, the synthetic challenges associated with these compounds have limited their exploration in chemical biology and drug discovery. In this study, we address this limitation by introducing a general Cu-catalyzed three-component carbonyl 1,2-transposition reaction, which proceeds via a P^V-oxirene intermediate. Our method employs I^III/P^V-hybrid ylides as carbene precursors to generate α-P^V-Cu-carbenes, which subsequently facilitate the formation of P^V-oxirene species. This intermediate undergoes regioselective ring-opening by carboxylate anions, followed by acylation of a third nucleophile, enabling the modular assembly of α-oxy carbonyl compounds. This strategy provides efficient access to α-oxy esters, amides, and thioesters, exhibiting broad tolerance to various functional groups. Furthermore, these compounds exhibit remarkable chemical versatility, as demonstrated in the synthesis of depsipeptides and late-stage drug modification, underscoring their applicability across diverse research areas. Our findings not only significantly expand the structural diversity of accessible α-oxy carbonyls but also introduce a versatile and biocompatible synthetic linkage for chemical synthesis.</p>